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PubMed2006

Prospective randomized comparison of progressive dilational vs forceps dilational percutaneous tracheostomy.

This trial prospectively compares two methods of percutaneous tracheostomy, both routinely used in ICU: the Ciaglia progressive dilational tracheostomy and the Griggs forceps dilational tracheostomy. One hundred patients were randomized using a single-blinded envelope method to receive progressive or forceps percutaneous tracheostomy performed at the bedside. Operative time, the occurrence of hypoxaemia or hypercapnia and complications were recorded. The progressive technique took longer than the forceps technique (median 7 (range 2-26) vs. 4 (1-16) minutes, P = 0.0005). Hypercapnia occurred in both groups but was more marked with the progressive technique (56 (16) vs. 49 (13) mmHg, P = 0.0082). Minor complications (minor bleeding, transient hypoxaemia, damage to posterior tracheal wall without emphysema) were also more frequent with the progressive technique (31 vs. 9 complications, P < 0.0001). Six major complications occurred with the progressive technique, none with the forceps technique (P = 0.0085): tension pneumothorax, posterior tracheal wall injury with subcutaneous emphysema, loss of airway with hypoxaemia, loss of stoma with impossible re-catheterization, and two conversions to another technique. In conclusion, progressive dilational tracheostomy took longer, caused more hypercapnia and more minor and major difficulties than forceps dilational tracheostomy.

Adult↗
PubMed2003

Elevated interleukin-7 levels not sufficient to maintain T-cell homeostasis during simian immunodeficiency virus-induced disease progression.

Elevated levels of interleukin 7 (IL-7) have been correlated with various T-cell depletion conditions, including HIV infection, and suggested as an indicator of HIV disease progression (AIDS and death). Here, the assessment of pathogenic simian immunodeficiency virus (SIVmac239) infection in rhesus macaques demonstrated a clear association between a significant elevation in IL-7 levels and disease progression. In 5 macaques that progressed to simian AIDS and death, elevated IL-7 levels were unable to restore T-cell homeostasis. In contrast, increased IL-7 levels were followed by relatively high and stable T-cell numbers in the SIV-infected macaques with a slow-progressing phenotype. Further, studies in sooty mangabeys that do not progress to simian AIDS and that maintain stable T-cell numbers despite high levels of viral replication support the importance of IL-7 and T-cell homeostasis in disease progression. These data suggest that during pathogenic SIV infection with high viral replication, elevated IL-7 levels are unable to recover T-cell homeostasis, thereby leading to disease progression. The utility of IL-7 as a potential immunotherapeutic agent to improve HIV/SIV-related T-cell depletion may therefore depend on controlling the pathogenic effects of viral replication prior to the administration of IL-7.

Animals↗
PubMed2006

Expression of hyaluronan in human tumor progression.

BACKGROUND: The development and progression of human tumors is accompanied by various cellular, biochemical and genetic alterations. These events include tumor cells interaction with extracellular matrix molecules including hyaluronan (HA). Hyaluronan is a large polysaccharide associated with pericellular matrix of proliferating, migrating cells. Its implication in malignant transformation, tumor progression and with the degree of differentiation in various invasive tumors has well accepted. It has been well known the role HA receptors in tumor growth and metastasis in various cancer tissues. Previously we have observed the unified over expression of Hyaluronic Acid Binding Protein (HABP), H11B2C2 antigen by the tumor cells in various types progressing tumor tissues with different grades. However, the poor understanding of relation between HA and HA-binding protein expression on tumor cells during tumor progression as well as the asymmetric observations of the role of HA expression in tumor progression prompted us to examine the degree of HA expression on tumor cells vs. stroma in various types of human tumors with different grades. METHODS: In the present study clinically diagnosed tumor tissue samples of different grades were used to screen the histopathological expression of hyaluronan by using b-PG (biotinylated proteoglycan) as a probe and we compared the relative HA expression on tumor cells vs. stroma in well differentiated and poorly differentiated tumors. Specificity of the reaction was confirmed either by pre-digesting the tissue sections with hyaluronidase enzyme or by staining the sections with pre-absorbed complex of the probe and HA-oligomers. RESULTS: We show here the down regulation of HA expression in tumor cells is associated with progression of tumor from well differentiated through poorly differentiated stage, despite the constant HA expression in the tumor associated stroma. CONCLUSION: The present finding enlighten the relative roles of HA expression on tumor vs. stroma during the progression of tumors.

Journal Article↗
PubMed2006

Corticotroph tumor progression after adrenalectomy in Cushing's Disease: A reappraisal of Nelson's Syndrome.

CONTEXT: Adrenalectomy is a radical treatment for hypercortisolism in Cushing's disease. However, it may lead to Nelson's syndrome, originally defined by the association of a pituitary macroadenoma and high plasma ACTH concentrations, a much feared complication. OBJECTIVE: The objective of the study was to reconsider Nelson's syndrome by investigating corticotroph tumor progression based on pituitary magnetic resonance imaging scan and search for predictive factors. DESIGN: This was a retrospective cohort study. SETTING: The complete medical records of Cushing's disease patients at Cochin Hospital were studied. PATIENTS: Patients included 53 Cushing's disease patients treated by adrenalectomy between 1991 and 2002, without previous pituitary irradiation. MEASUREMENTS: Clinical data, pituitary magnetic resonance imaging data, and plasma ACTH concentrations for all patients and pituitary gland pathology data for 25 patients were recorded. Corticotroph tumor progression-free survival was studied by Kaplan-Meier, and the influence of recorded parameters was studied by Cox regression. INTERVENTION: There was no intervention. RESULTS: Corticotroph tumor progression ultimately occurred in half the patients, generally within 3 yr after adrenalectomy. A shorter duration of Cushing's disease (adjusted hazard ratio: 0.884/yr), and a high plasma ACTH concentration in the year after adrenalectomy [adjusted hazard ratio per 100 pg/ml (22 pmol/liter): 1.069] were predictive of corticotroph tumor progression. In one case, corticotroph tumor progression was complicated by transitory oculomotor nerve palsy. During follow-up, corticotroph tumor progression was associated with the increase of corresponding ACTH concentrations (odds ratio per 100 pg/ml of ACTH variation: 1.055). CONCLUSION: After adrenalectomy in Cushing's disease, one should no longer wait for the occurrence of Nelson's syndrome: modern imaging allows early detection and management of corticotroph tumor progression.

Adolescent↗
PubMed1988

Risk factors for progression in Parkinson's disease.

Using case-control methodology, we assessed prevalence and duration of exposure to putative risk factors for rapid progression of Parkinson's disease (PD) in patients not taking levodopa or direct dopamine agonists. We identified 31 patients termed "rapidly progressive" who were stage I or II (Hoehn and Yahr) on their first visit to our center and who progressed to stage III during the study period; we pair-matched this group with 31 "slowly progressive" patients who had the same symptom duration and the same Hoehn and Yahr stage at study entry, but whose parkinsonism did not progress to stage III during the study. Only age of PD onset was associated with different rates of PD progression; older patients at PD onset progressed more rapidly than younger patients.

Age Factors↗
PubMed1991

A placebo-controlled, double-blind, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis.

We found Cop 1 to be effective and relatively safe in a previous (exacerbating-remitting) clinical trial. This current trial involves 106 chronic-progressive patients. The major end point, confirmed progression of 1.0 or 1.5 units (depending on baseline disability) on the Kurtzke Expanded Disability Status Scale, was observed in nine (17.6%) treated and 14 (25.5%) control patients. The differences between the overall survival curves were not significant. Progression rates at 12 and 24 months were higher for the placebo group (p = 0.088) with 2-year probabilities of progressing of 20.4% for Cop 1 and 29.5% for placebo. We found a significant difference at 24 months between placebo and Cop 1 at one but not the other center. Two-year progression rates for two secondary end points, unconfirmed progression, and progression of 0.5 EDSS units, (p = 0.03) are significant.

Chronic Disease↗
PubMed1999

Primary and transitional progressive MS: a clinical and MRI cross-sectional study.

BACKGROUND: Ten percent of patients with MS have a progressive course from onset with no history of relapses or remissions. A smaller subgroup follow a similar progressive course but have a single relapse at some point (transitional progressive [TP] MS). To date these patients have been excluded from receiving licensed treatments for MS and from most therapeutic trials. OBJECTIVE: To document the clinical and MRI characteristics of a large cohort of progressive patients, including 158 with primary progressive (PP) MS and 33 with TPMS. Data from a small reference group of 20 patients with secondary progressive (SP) MS are also presented for reference. METHODS: Patients were recruited from six European centers. All underwent a clinical assessment including scoring on the Expanded Disability Status Scale (EDSS) and MRI of the brain and spinal cord. RESULTS: The men-to-women ratio was 81:77 (51% men) in the PP group, 14:19 (42% men) in the TP group, and 5:15 (25% men) in the SP group. The mean age at disease onset was significantly higher in the PP group than it was in the other two groups (PP 40.2 years, TP 34.9 years, SP 28.7 years). On MRI the PP group had lower mean brain T2 and T1 hypointensity lesion loads than the SP group (T2 12.02 versus 27.74 cm3, p = 0.001; T1 4.34 versus 7.04 cm3, p = 0.015). The SP and TP cohorts had significantly more T2-weighted lesions in the spinal cord than the PP patients, and the SP cohort had the greatest degree of atrophy. There was a correlation in the PP and TP patients between EDSS score and brain and spinal cord atrophy (r = 0.3, 0.2, p < or = 0.006) but not with brain lesion load. The PP and TP patients who presented with spinal cord pathology had significantly lower brain T2 and T1 lesion loads than those with non-spinal cord presentations (p = 0.002). CONCLUSIONS: The monitoring of disease progression in PPMS is difficult, although measures of atrophy correlate with the EDSS and appear most promising. This study increases our understanding of this unique patient group, which will be further expanded with the acquisition of serial data.

Adult↗
PubMed2000

Whole brain volume changes in patients with progressive MS treated with cladribine.

OBJECTIVE: To compare changes in whole brain volume measured using MRI scans in patients with progressive MS enrolled in a double-blind, placebo-controlled trial assessing the efficacy of two doses of cladribine (0.7 and 2.1 mg/kg) and to assess the correlations between change in whole brain volume and change in other conventional MRI measures. BACKGROUND: Measuring brain parenchymal volumes is an objective and reliable surrogate for the destructive pathologic process in MS. The dynamics and the mechanisms of tissue loss in progressive MS are unclear. METHODS: Whole brain volumes were measured using postcontrast T1-weighted scans with 3 mm slice thickness from 159 patients with progressive MS (70% secondary progressive and 30% primary progressive) enrolled in a double-blind, placebo-controlled trial of 12-month duration. RESULTS: Whole brain volumes were similar in the placebo and cladribine-treated patients on the baseline scans. A significant decrease of brain volume over time was observed both in the entire population of patients (p = 0.001) and in the placebo patients in isolation (p = 0.04). No significant treatment effect of either dose of cladribine on brain volume changes over time was found. In the 54 patients who received placebo, the change in brain volume was not significantly correlated with other MRI measures at baseline (enhancing lesion number and volume and T2-hyperintense and T1-hypointense lesion volumes) or at follow-up (cumulative number of enhancing lesions and absolute and percentage changes of enhancing T2- and T1-hypointense lesion volumes). CONCLUSIONS: This study shows in a large cohort of patients that brain parenchymal loss occurs, even over a short period of time, in progressive MS and that cladribine is not able to alter this process significantly. It also suggests that MRI-visible inflammation and new lesion formation has a marginal role in the development of brain atrophy in patients with progressive MS.

Brain↗
PubMed1998

Cyclic AMP delays G2 progression and prevents efficient accumulation of cyclin B1 proteins in mouse macrophage cells.

In mouse macrophage cells, the increase of the intracellular cAMP level activates protein kinase A (PKA) and results in inhibition of cell cycle progression in both G1 and G2/M phases. G1 arrest is mediated by a cdk inhibitor, p27Kip1, which prevents G1 cyclin/cdk complexes from being activated in response to colony stimulating factor-1, whereas inhibition of G2/M progression has not been fully elucidated. In this report we analyzed the effect of cAMP on G2/M progression in a mouse macrophage cell line, BAC1.2F5A. Flow cytometric analysis and mitotic index measurement using both synchronized and asynchronized cells revealed that addition of cAMP-elevating agents (8-bromoadenosine 3':5'-cyclic monophosphate and 3-isobutyl-methyl-xanthine), although they did not affect S phase progression or M/G1 transition, temporarily arrested cells in G2 but eventually the cells proceeded to M phase, resulting in about 4 hours delay of G2 progression. Timing of cyclin B1/Cdc2 kinase activation was also retarded by about 4 hours, which was accompanied by inhibition of efficient accumulation of cyclin B1 proteins. Initial induction and accumulation of cyclin B1 mRNA were not hampered, but the half life of cyclin B1 proteins was significantly shorter during G2 phase in the presence of cAMP-elevating agents compared with that of the cells blocked from progressing through M phase by nocodazole. These results imply that the cAMP/PKA pathway regulates G2 phase progression by altering the stability of a crucial cell cycle regulator.

Animals↗
PubMed1993

Progression of the curve in boys who have idiopathic scoliosis.

The prevalence of curve progression was evaluated in 210 boys who had idiopathic scoliosis. A minimum age of eight years, a deformity of at least 10 degrees, and radiographic follow-up of one year or progression of the curve within the first year of follow-up were the criteria for inclusion in the study. Of the 210 patients, sixty-eight (32 per cent) had progression of 10 degrees or more. Four of the five patients who had had an initial curve of 50 degrees or more subsequently had a spinal arthrodesis. The risk of progression was significantly greater for patients who were at an earlier Risser stage (p < 0.002) and for those who were younger (p < 0.005). The risk of progression was also greater for patients who had had a larger curve at the time of presentation; of the sixty-three boys for whom the Risser grade was 1, 2, 3, 4, or 5 when they were first seen and who had a curve of 25 degrees or more, twenty (32 per cent) had progression, compared with only two (5 per cent) of the thirty-eight who had a Risser grade of 1, 2, 3, 4, or 5 and a curve of 24 degrees or less. Of the thirty-four patients for whom the Risser grade was 4 when they were first seen, five (15 per cent) had progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2004

Slowing the progression of adult chronic kidney disease: therapeutic advances.

When kidney disease of any aetiology results in substantial loss of nephrons, a common clinical syndrome, characterised by hypertension, proteinuria and a progressive decline in renal function, ensues. This observation suggests that common mechanisms may contribute to progressive renal injury and that therapeutic interventions that inhibit these common pathways may afford renal protection. Research to date has identified several mechanisms that may contribute to progressive renal injury including glomerular haemodynamic changes, multiple effects of angiotensin II and detrimental effects of excessive filtration of plasma proteins by injured glomeruli. Clinical trials over the past decade have identified several interventions that are effective in slowing the rate of progression of chronic kidney disease (CKD). The use of ACE inhibitors, angiotensin receptor antagonists or a combination of the two should be regarded as fundamental to any therapy for slowing the rate of CKD progression. Hypertension should be treated aggressively to achieve a blood pressure target of < 130/80 mm Hg. Reduction of proteinuria to < 0.5 g/day should be regarded as an independent therapeutic goal. Although inconclusive, there is some evidence to support moderate dietary protein restriction to 0.6 g/kg/day in appropriate patients. Hyperlipidaemia may contribute to CKD progression and should be treated to reduce cardiovascular risk and potentially improve renal protection. Smoking cessation should be encouraged and, where necessary, assisted. Among diabetic patients tight glycaemic control should be achieved (glycosylated haemoglobin < 7%). These interventions are simple and relatively inexpensive. If applied to all patients with CKD they will result in substantial slowing of renal function decline in many patients and thereby reduce the number who progress to end-stage renal disease and require renal replacement therapy.

Adult↗
PubMed1995

Clinical features of progressive lacunar infarction--retrospective analysis of patients with motor syndromes.

The clinical features of progressive lacunar infarction were analyzed in 20 patients with lacunar infarction. Seven of the 20 patients experienced paresis progression and the remaining 13 patients had a stable course. The mean age of progressive lacunar infarction patients (78.6 +/- 4.30 yrs) was significantly higher than that of stable lacunar infarction patients (65.1 +/- 7.68 yrs) (p < 0.01). Patients presenting with pure motor stroke were more likely to have progressive stroke (7/13) than those presenting with sensorimotor stroke (0/7) (p < 0.05). Paresis aggravation began on Day 1 and ceased on Day 2 in most patients. Progressive paresis began to improve after reaching the nadir. Hemiparesis was only slightly worse after 1 month compared with that on admission. Older patients are more likely to have a progressive course. Paresis progression in lacunar patients does not preclude the possibility of recovery and is not necessarily associated with a poor prognosis.

Aged↗
PubMed1999

[Low-dose weekly methotrexate therapy for progressive neuro-Behçet's disease].

Among a variety of central nervous system (CNS) manifestations of Behçet's disease, the most serious one is progressive dementia. However, there has been no effective treatment to prevent the progression of dementia. The present studies have examined the efficacy of low-dose weekly methotrexate therapy for the progressive dementia in Behçet's disease. Six patients with the progressive type of neuro-Behçet's disease were treated with low-dose weekly methotrexate (7.5-15 mg/week). Neurological findings, psychological findings, brain MRI and IL-6 in cerebrospinal fluid were evaluated at the start and one year after the initiation of the therapy. All the 6 patients were refractory to the conventional therapy for neuro-Behçet's disease. The progression of neuropsychological abnormalities such as dementia was not recognized after one year from the initiation of methotrexate therapy. Consistently, IL-6 levels in cerebrospinal fluid were significantly decreased after one year from the initiation of therapy. Six months after the discontinuation of low-dose weekly methotrexate, progression of neuropsychological abnormalities such as dementia was recognized, and IL-6 levels in cerebrospinal fluid were significantly increased. These findings may suggest the suppression of the ongoing inflammatory process in the intracranial lesions by methotrexate. These results suggest that low-dose weekly methotrexate therapy may be a new promising method for the treatment of the progressive type of neuro-Behçet's disease.

Behcet Syndrome↗
PubMed1989

Radioassay determination of insulin autoantibodies in NOD mice. Correlation with increased risk of progression to overt diabetes.

In an initial cross-sectional study, 29 female and 25 male nondiabetic weaned nonobese diabetic (NOD) mice of various ages (age range 30-300 days, mean 108 +/- 10 days) and 11 unweaned NOD pups were evaluated for competitive insulin autoantibodies (CIAAs) with a fluid-phase radioassay. Eleven of 54 (20%) weaned NOD mice had CIAA levels above the range (greater than 39 nU/ml) of 81 control mice. The group of NOD mice that progressed to diabetes had a significantly higher level of CIAAs than NOD mice that did not progress to diabetes (NOD mice progressing to diabetes: CIAA 63 +/- 12 nU/ml; NOD mice not progressing to diabetes: CIAA 8 +/- 4 nU/ml; P less than .02). Seven of 11 (64%) NOD mice having CIAA concentrations exceeding the normal range progressed to diabetes, whereas only 4 of 43 (9%) NOD mice progressed to diabetes without detection of elevated CIAAs (Fisher's exact test, P less than .0005). The relative risk of progressing to overt diabetes with CIAA levels greater than 39 nU/ml was therefore 17 (P less than .005), giving a positive predictive value of 64%, a negative predictive value of 91%, and an overall accuracy of 85%. None of 11 unweaned NOD pups had CIAA levels above the normal range (mean -9.4 +/- 4.9 nU/ml). At 6 wk of age, 37% of female NOD mice were CIAA+, whereas none of the male animals exceeded the normal range at this age (38 +/- 13 vs. 5 +/- 6 nU/ml, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

High risk of progression to NIDDM in South-African Indians with impaired glucose tolerance.

A four-yr prospective study was undertaken to examine the natural history of IGT in 128 South-African Indians classified as such at year 0 of the study, based on WHO criteria. Subjects were reexamined at year 1 and year 4. Of the 113 subjects who completed the study, 50.4% progressed to NIDDM (rate of progression 12.6%/yr), 24.8% persisted with IGT, and 24.8%, reverted to NGT. The majority (72%) who progressed to NIDDM did so in year 1. At year 1, 47 subjects were still classified as IGT; of the 40 subjects completing the study, 16 subjects (40%) progressed to NIDDM, 17 subjects (42.5%) persisted with IGT, and 7 subjects (17.5%) reverted to NGT. Examination of risk factors predictive of subsequent progression to NIDDM was undertaken by analysis of baseline variables in two ways: When year 0 was used as baseline (in 113 IGT0 subjects), significant predictive risk factors were the FPG and 2-h plasma glucose concentrations. All subjects who at year 0 had 2-h plasma glucose > or = 10.2 and < 11.1 mM or FPG > or = 7.3 but < 7.8 mM, subsequently progressed to NIDDM. When year 1 was used as baseline (40 IGT1 subjects), 90-min plasma glucose concentration (midtest level) was found to be a significant risk factor for development of NIDDM. In conclusion, this study has demonstrated that in South-African Indians with IGT, the majority (50.4%) progress to NIDDM within 4 yr; significant predictors of subsequent diabetes are the baseline fasting and 2-h plasma glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

[The relative assessment of atherosclerosis in vessels of major organs and its factors for progression].

In order to study the relative assessment of atherosclerosis among arteries of various organ (coronary, aortic, peripheral and cerebral artery), 94 patients aged 43-69 underwent examination by coronary angiography (CAG), pulse wave velocity (PWV), ankle pressure index (API) and funduscopy simultaneously. The severity of coronary sclerosis was determined by the coronary atherosclerotic index (CAI) which was based on the size and number of stenotic lesions, which that of funduscopic findings was evaluated using Scheies' score (S+H). The relationship between risk factors of atherosclerosis and each value for the examinations (CAI, PWV, API, S+H) were studied. Furthermore, subjects were divided into two groups of normal or early change groups and a progressive group based on the degree of atherosclerosis. Then, the difference of atherosclerosis in each vessel of major organs was compared. A positive correlation between PWV and age, and a negative correlation between API and age were noted (p < 0.01, p < 0.05). A higher prevalence of hypertension in groups of progressive PWV or API were observed (p < 0.05). Total cholesterol in the CAI progressive group was significantly higher than in the normal group (p < 0.005), and it became higher in relation to the progression of PWV or API (p < 0.001). HDL-C in the progressive groups of CAI, PWV API and S+H were significantly lower (p < 0.05, p < 0.05, p < 0.02, p < 0.01). On the other hand, glucose intolerance influenced the progression of CAI, PWV, API and S+H, statistically. In subjects whose age was limited to between 55-64, statistically significant correlations were noted between any pair of examinations among CAI, PWV, API and S+H. The percentage of API and S+H progressive groups were lower in CAI normal of PWV early change groups, suggesting earlier sclerotic change of the coronary artery or aorta than that of peripheral or cerebral artery. These results demonstrate that the atherosclerosis in major vessels could be assessed relatively using a non pathological process, which supports the usefulness of these examinations in clinical practice.

Adult↗
PubMed1990

[Statistical evaluation of determinants of progression of superficial bladder cancer by proportional hazards model].

To evaluate clinical and pathological factors present at the initial consultation which affect disease progression, we reviewed data from 223 patients with superficial bladder cancer (pTa and pT1) who were initially treated at Nagoya University Hospital between January 1973 and December 1987. The factors included in the present analysis were age, sex, symptoms, interval between initial symptoms and first consultation, location of tumor, size, number, endoscopic shape, histological pattern of growth, grade and stage. The median duration of the follow-up after initial treatment was 46 months. Of the 223 patients, 17 died: 8 (3.6%) of bladder cancer and the remaining 9 (4.0%) of unrelated causes. Disease progression developed in 12 patients (5.4%): muscle invasion of the bladder wall in 11 and lung metastasis in one. The interval between initial treatment and progression ranged from 4 to 108 months, with a median of 11.5 months. Of the 12 patients, 9 (75%) had disease progression within 2 years. Progression was significantly associated with poor prognosis (p less than 0.001): the 5-year actuarial survival rates were 47.1% and 92.8% in patients with and without progression, respectively. Univariate analysis by Cox's proportional hazards model demonstrated that characteristics such as irritative bladder symptoms, higher-grade tumors, invasion into lamina propria, and nonpapillary growth seen at initial consultation were significantly related to disease progression. Cox's proportional hazards model produced hazard ratios of 10.2 in irritative bladder symptoms (yes vs. no), 6.3 in histological grade (grade 3 vs. grades 0-2), 4.9 in stage (pT1 vs. pTa), and 4.7 in pattern of growth (papillary vs. nonpapillary).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

CD4+ lymphocytes are an incomplete surrogate marker for clinical progression in persons with asymptomatic HIV infection taking zidovudine.

OBJECTIVE: To determine the extent to which lymphocytes, particularly those with the CD4 surface antigen, are a surrogate marker for the development of the acquired immunodeficiency syndrome (AIDS) in persons with asymptomatic human immunodeficiency virus (HIV) infection. DESIGN: Analysis of data from the AIDS Clinical Trials Group Protocol 019, a placebo-controlled, double-blind, randomized trial. SETTING: University-based referral centers. PATIENTS: Asymptomatic HIV-infected patients with 500 or fewer CD4+ cells/mm3 at baseline who were given placebo (350 patients) or one of two daily doses of zidovudine (725 patients). MEASUREMENTS: Baseline and interim measurements of CD4+ and other leukocytes were assessed. Patients were followed for progression to AIDS. RESULTS: Patients' lymphocyte levels were correlated with progression to AIDS (P < 0.001; relative risk for each depletion of 50 CD4+ cells/mm3, 1.75; 95% CI, 1.53 to 2.01); however, only a small portion (0% to 37%) of the effect of zidovudine on this progression was statistically explained by its effect on CD4+ lymphocyte levels. A substantial portion of zidovudine's effect on delaying progression to AIDS that was independent of the levels of these markers occurred within the first 16 weeks of therapy. In patients who had not progressed to AIDS by week 16, most of the subsequent zidovudine effect in reducing the risk for progression could be explained by its effect on net CD4+ percent (percentage of CD4+ lymphocytes among all leukocytes) for the first 16 weeks of therapy. CONCLUSION: Levels of CD4+ lymphocytes are an incomplete surrogate marker for progression to AIDS, and the association is especially weak during the first 16 weeks of zidovudine therapy.

Acquired Immunodeficiency Syndrome↗